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Protein / target

DNA (cytosine-5)-methyltransferase 1

Encoded byDNMT1P26358Homo sapiensSwiss-Prot
UniProt: P26358Ensembl: ENSG00000130816HGNC: HGNC:2976NCBI Gene: 1786
Clinically validated
Therapeutic maturity
2
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

DNA (cytosine-5-)-methyltransferase

Strongest disease association

Neoplasms

Via encoding gene DNMT1 · Genetic evidence · score 0.26

Therapeutic position

Established drug target

Small molecules

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

DNA methyltransferase that methylates CpG residues.

View complete UniProt function annotation

DNA methyltransferase that methylates CpG residues (PubMed:17200670, PubMed:18754681, PubMed:21745816, PubMed:26070743). Preferentially methylates hemimethylated DNA (PubMed:21745816, PubMed:26070743). Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is essential for epigenetic inheritance (PubMed:17200670, PubMed:21745816). Associates with chromatin during G2 and M phases to maintain DNA methylation independently of replication (PubMed:21745816). It is responsible for maintaining methylation patterns established in development (PubMed:21745816). DNA methylation is coordinated with methylation of histones (PubMed:16357870). Mediates transcriptional repression by direct binding to HDAC2 (PubMed:10888872). In association with DNMT3B and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9 (PubMed:18413740). Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306). Also required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306)

Subcellular location

NucleusChromosome
Domains and Gene Ontology detail (32)

Domains & features

DMAP1-bindingRFTSBAH 1BAH 2SAM-dependent MTase C5-type

Gene Ontology

  • Cheterochromatin
  • Cmitochondrion
  • Cnucleoplasm
  • Cnucleus
  • Cpericentric heterochromatin
  • Creplication fork
  • FDNA (cytosine-5-)-methyltransferase activity
  • FDNA binding
  • FDNA-methyltransferase activity
  • Fhistone H3K14ub reader activity
  • Fhistone H3K18ub reader activity
  • Fhistone H3K23ub reader activity

1616 aa · 183 kDa · 3 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Transcriptional regulationUniProt · GOMetabolic enzyme activityGO
View supporting evidence

Transcriptional regulation

  • ·DNA methyltransferase that methylates CpG residues (PubMed:17200670, PubMed:18754681, Pu…
  • ·DNA-templated transcription
  • ·negative regulation of gene expression
  • ·negative regulation of gene expression via chromosomal CpG island methylation

Metabolic enzyme activity

  • ·DNA (cytosine-5-)-methyltransferase activity
  • ·DNA-methyltransferase activity

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Approved medicines with mapped indications

2 medicines · 5 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Myelodysplastic Syndromes2 medicines
azacitidinedecitabine
Anemia1 medicine
decitabine
Leukemia, Myeloid1 medicine
decitabine
Leukemia, Myeloid, Acute1 medicine
azacitidine
Broader indication categories (1)
Neoplasms2 medicines
azacitidinedecitabine

Broad umbrella indications (e.g. “Neoplasms”). Shown here because every medicine also appears under a more specific disease above — kept for completeness, de-emphasised for clarity.

Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

2

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

azacitidine
Narrow target profileApprovedInhibitor

DNA (cytosine-5)-methyltransferase 1 inhibitor

Indicated for Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Neoplasms

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

decitabine
Narrow target profileApprovedInhibitor

DNA (cytosine-5)-methyltransferase 1 inhibitor

Indicated for Anemia, Leukemia, Myeloid, Myelodysplastic Syndromes, Neoplasms

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene DNMT1

Gene-level evidence surfaced through the gene DNMT1that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Neoplasms
0.83Well supported

Clinical evidence dominant · Open Targets 0.61

Leukemia, Myeloid, Acute
0.77Well supported

Clinical evidence dominant · Open Targets 0.62

Myelodysplastic syndrome
0.76Well supported

Clinical evidence dominant · Open Targets 0.62

Chronic myelomonocytic leukemia
0.74Moderately supported

Clinical evidence dominant · Open Targets 0.60

Anemia
0.62Moderately supported

Clinical evidence dominant · Open Targets 0.50

View evidence synthesis (5)
NeoplasmsWell supported
0.83
agreement 0.73–0.93
Clinical44%Pathway26%Genetic20%Literature11%

Open Targets aggregate 0.61 · 4 independent evidence families

Leukemia, Myeloid, AcuteWell supported
0.77
agreement 0.62–0.93
Clinical84%Literature16%

Open Targets aggregate 0.62 · 2 independent evidence families

Myelodysplastic syndromeWell supported
0.76
agreement 0.60–0.91
Clinical91%Literature9%

Open Targets aggregate 0.62 · 2 independent evidence families

Chronic myelomonocytic leukemiaModerately supported
0.74
agreement 0.58–0.89
Clinical99%Literature1%

Open Targets aggregate 0.60 · 2 independent evidence families

AnemiaModerately supported
0.62
agreement 0.46–0.77
Clinical99%Literature1%

Open Targets aggregate 0.50 · 2 independent evidence families

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Leukemia, Myeloid, Acute0.62
Myelodysplastic syndrome0.62
Neoplasms0.61
Chronic myelomonocytic leukemia0.60
Anemia0.50
Leukemia, Myeloid0.49

Drug development

2 compounds recorded · 2 approved

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 2 drugs that target this protein in Forefront's canonical graph (2 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (2)
DECITABINEApproval
AZACITIDINEApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Strong

Approved Drug and Structure with Ligand support this modality.

Protein degraders — Emerging

Feasibility evidence (uniprot ubiquitination and database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (9)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

REMAIN1: Relapse Prevention With Maintenance Oral Azacitidine in Transplant Eligible Patients With Acute Myeloid Leukemia Not Proceeding to Transplant Due to Racial or Socioeconomic DisparitiesPHASE4

RECRUITING · via azacitidine · NCT06370000

Venetoclax+Decitabine+Busulfan+Fludarabine (VEN+DAC+Bu2Flu4) vs Busulfan+Fludarabine Conditioning Regimen (Bu2Flu5 ) for Older Patients With Myeloid Malignancies Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT)PHASE2/PHASE3

NOT_YET_RECRUITING · via decitabine · NCT07052422

A Phase 4 Study of Venetoclax in Combination With Azacitidine in Newly Diagnosed Subjects With Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy in ChinaPHASE4

ACTIVE_NOT_RECRUITING · via azacitidine · NCT05144243

A Phase II/III Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of BL-M11D1 for Injection in Combination With Cytarabine + Daunorubicin or Venetoclax + Azacitidine in Patients With Acute Myeloid LeukemiaPHASE2/PHASE3

NOT_YET_RECRUITING · via azacitidine · NCT07255872

View all trials (26)
A Randomized Phase III, Global, Multicentre, Open Label Clinical Trial Comparing Venetoclax Azacytidine and Quizartinib Versus Venetoclax and Azacytidine in Newly Diagnosed Acute Myeloid Leukemia Patients Unelegible for Standard Induction ChemotherapyPHASE3

NOT_YET_RECRUITING · via azacitidine · NCT07478991

A Randomized, Open-labelled, Multicenter Trial Evaluating Efficacy and Safety of A Reduced Venetoclax Exposure To Seven Days Versus Standard Continuous Venetoclax Exposure Combined With Azacitidine in Treatment Naïve Subjects With Acute Myeloid Leukemia Who Are Ineligible for Intensive InductionPHASE3

NOT_YET_RECRUITING · via azacitidine · NCT07082452

A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Study of Bleximenib, Venetoclax and Azacitidine for the Treatment of Participants With Newly Diagnosed Acute Myeloid Leukemia Harboring KMT2A Rearrangements or NPM1 Mutations Who Are Ineligible for Intensive ChemotherapyPHASE3

RECRUITING · via azacitidine · NCT06852222

A Phase 3, Multicenter, Open Label, Randomized, Non-comparative Two-arm Study of Ivosidenib (IVO) Monotherapy and Azacitidine (AZA) Monotherapy in Adult Patients With Hypomethylating Agent (HMA) Naive Myelodysplastic Syndromes (MDS) With an Isocitrate Dehydrogenase-1 (IDH1) Mutation (PyramIDH Study)PHASE3

RECRUITING · via azacitidine · NCT06465953

A Global, Multicenter, Randomized, Double-blind, Phase 3 Pivotal Registrational Clinical Study of APG-2575 (Lisaftoclax) Combined With Azacitidine in Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia (GLORA-3)PHASE3

RECRUITING · via azacitidine · NCT06389292

Decitabine and Umbilical Cord Blood for Poor Graft Function Post Allogenic Hematopoietic Stem Cell TransplantationPHASE3

NOT_YET_RECRUITING · via decitabine · NCT05669079

Low Dose Decitabine for Poor Graft Function Post Allogenic Hematopoietic Stem Cell TransplantationPHASE3

NOT_YET_RECRUITING · via decitabine · NCT05907499

Randomized, Multicenter, Phase 3 Study of Azacytidine (AZA) + Venetoclax as Maintenance Therapy in Patients With AML in Remissionin Younger Adults With Favorable-risk AML in First Remission After Conventional ChemotherapyPHASE2/PHASE3

RECRUITING · via azacitidine · NCT05404906

A Phase II/III Randomized Study of R-MiniCHOP With or Without CC-486 (Oral Azacitidine) in Participants Age 75 Years or Older With Newly Diagnosed Diffuse Large B Cell Lymphoma, Grade IIIB Follicular Lymphoma, Transformed Lymphoma, and High-Grade B-Cell Lymphomas With MYC AND BCL2 and/or BCL6 RearrangementsPHASE2/PHASE3

ACTIVE_NOT_RECRUITING · via azacitidine · NCT04799275

A Randomized, Open-Label Study of the Efficacy and Safety of Galinpepimut-S (GPS) Maintenance Monotherapy Compared to Investigator's Choice of Best Available Therapy in Subjects With Acute Myeloid Leukemia Who Have Achieved Complete Remission After Second-Line Salvage TherapyPHASE3

ACTIVE_NOT_RECRUITING · via azacitidine · NCT04229979

A Randomized Phase III, Multicentre, Open Label Clinical Trial Comparing Azacitidine Plus Pevonedistat Versus Azacitidine in Older/Unfit Patients With Newly Diagnosed Acute Myeloid Leukemia Who Are Ineligible for Standard Induction ChemotherapyPHASE3

ACTIVE_NOT_RECRUITING · via azacitidine · NCT04090736

A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study of AG-120 in Combination With Azacitidine in Subjects ≥ 18 Years of Age With Previously Untreated Acute Myeloid Leukemia With an IDH1 MutationPHASE3

ACTIVE_NOT_RECRUITING · via azacitidine · NCT03173248

A Randomized, Double-Blind, Placebo Controlled Phase 3 Study of Venetoclax in Combination With Azacitidine Versus Azacitidine in Treatment Naïve Subjects With Acute Myeloid Leukemia Who Are Ineligible for Standard Induction TherapyPHASE3

ACTIVE_NOT_RECRUITING · via azacitidine · NCT02993523

A Phase 1/2 Study of Pacritinib in Combination With Azacitidine for the Treatment of IPSS-M Moderate Low to Very High Risk Myelodysplastic SyndromePHASE1/PHASE2

NOT_YET_RECRUITING · via azacitidine · NCT07387354

Pilot Single Arm Phase 2 Study of Olutasidenib in Relapsed IDH1 Mutated AML Patients Who Have Previously Received VenetoclaxPHASE2

RECRUITING · via azacitidine · NCT07471841

Clinical Study of Sonrotoclax Combined With Azacitidine Plus Individualized Targeted Drugs in the Treatment of Newly Diagnosed Adult Acute Myeloid LeukemiaPHASE2

RECRUITING · via azacitidine · NCT07548710

A Prospective, Open-Label, Single-Arm, Two-Cohort Phase 2 Clinical Study to Evaluate the Efficacy and Safety of Bcl-2 Inhibitor Combined With Azacitidine in the Treatment of Newly Diagnosed Mixed Phenotype Acute LeukemiaPHASE2

NOT_YET_RECRUITING · via azacitidine · NCT07573670

A Multi-Site Break Through Cancer Trial: Targeting Measurable Residual Disease in Patients With Acute Myeloid Leukemia: A Phase 1/2 Study of Tagraxofusp, Azacitidine, and VenetoclaxPHASE1/PHASE2

RECRUITING · via azacitidine · NCT07148180

A Phase II Study of IDH1 Inhibition With Ivosidenib as Maintenance Therapy After Ivosidenib, Azacitidine, and Venetoclax for Acute Myeloid LeukemiaPHASE2

RECRUITING · via azacitidine · NCT07392242

Clinical Study on the Efficacy and Safety of Zeprumetostat, Azacitidine Combined With Mitoxantrone Hydrochloride Liposome in Relapsed/Refractory Peripheral T-Cell Lymphoma.PHASE2

RECRUITING · via azacitidine · NCT07372352

Sequential Decitabine in Combination With FLAG-Ida Followed Immediately by Reduced-Intensity Conditioning (RIC) Allogeneic Hematopoietic Cell Transplantation (DEC-FLAG-Ida/RIC) for Adults With Myeloid Malignancies at High Risk of Relapse: A Phase 1/2 StudyPHASE1/PHASE2

RECRUITING · via decitabine · NCT06928662

A Prospective Single-Arm Clinical Study of Venetoclax Combined With Azacitidine, Chidamide, Vindesine, and Dexamethasone in Newly Diagnosed ETP-ALL Like PatientsPHASE2

RECRUITING · via azacitidine · NCT07159620

AZA Combined with R-GemOx for the Initial Treatment of Elderly DLBCL: an Open, Single-arm, Multicenter Clinical StudyPHASE2

NOT_YET_RECRUITING · via azacitidine · NCT06778902

A Multicenter, Single-arm I/II Clinical Study of Olverembatinib Combined With Venetoclax and Azacitidine in in Blast Phase Ph Chromosome- Chronic Myeloid LeukemiaPHASE1/PHASE2

RECRUITING · via azacitidine · NCT06757855

A Randomized Phase II Study of Venetoclax and HMA-Based Therapies for the Treatment of Older and Unfit Adults With Newly Diagnosed FLT3-Mutated Acute Myeloid Leukemia (AML): A MyeloMATCH SubstudyPHASE2

RECRUITING · via azacitidine · NCT06317649

A Randomized Phase II Study Comparing Cytarabine + Daunorubicin (7 + 3) vs (Daunorubicin and Cytarabine) Liposome, Cytarabine + Daunorubicin + Venetoclax, Azacitidine + Venetoclax, and (Daunorubicin and Cytarabine) Liposome + Venetoclax in Patients Aged 59 or Younger Who Are Considered High-Risk (Adverse) Acute Myeloid Leukemia As Determined by MYELOMATCH; A MYELOMATCH SubStudyPHASE2

RECRUITING · via azacitidine · NCT05554406

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Trial status changed2026-08-25

    Phase I/II Study of Neoadjuvant Inhaled Azacytidine With Platinum-Based Chemotherapy and Durvalumab (MEDI4736) - a Combined Epigenetic-Immunotherapy (AZA-AEGEAN) Regimen for Operable Early-Stage Non-Small Cell Lung Cancer (NSCLC)

    Status changed to Suspended · ClinicalTrials.gov · via azacitidine

  2. Trial status changed2026-08-20

    A Pilot Study to Evaluate the Feasibility of Post-Hematopoietic Stem Cell Transplant Prophylaxis With Decitabine Combined With Filgrastim for Children and Young Adults With AML, MDS and Related Myeloid Malignancies

    Status changed to Active, not recruiting · ClinicalTrials.gov · via decitabine

  3. Trial status changed2026-07-31

    Study of Cladribine+Venetoclax After Failure of Venetoclax+Hypomethylating Agent in Monocytic AML

    Status changed to Active, not recruiting · ClinicalTrials.gov · via azacitidine

  4. Trial status changed2026-07-14

    Phase 1b Study of Pembrolizumab, Decitabine +/- Venetoclax Combination Therapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

    Status changed to Suspended · ClinicalTrials.gov · via decitabine

  5. Label change2026-06-09

    Label change: AZACITIDINE (ANDA204949)

    fda · regulatory · fda · via azacitidine

  6. Label change2026-06-09

    Label change: AZACITIDINE (ANDA204949)

    fda · regulatory · fda · via azacitidine

  7. Label change2026-06-09

    Label change: AZACITIDINE (ANDA204949)

    fda · regulatory · fda · via azacitidine

  8. Regulatory approval2024-01-05

    Approval: Azacitidine Kabi (EMA)

    ema · regulatory · ema · via azacitidine

  9. New publication2021-08-23
    Results of a randomized phase 3 study of oral sapacitabine in elderly patients with newly diagnosed acute myeloid leukemia (SEAMLESS).

    Cancer · 2021 · 6 citations · Europe PMC · via decitabine

  10. New publication2021-03-01
    Low-dose decitabine for refractory prolonged isolated thrombocytopenia after HCT: a randomized multicenter trial.

    Blood advances · 2021 · 18 citations · Europe PMC · via decitabine

  11. New publication2009-12-21
    Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2010 · 701 citations · Europe PMC · via azacitidine

  12. New publication2009-02-21
    Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study.

    The Lancet. Oncology · 2009 · 1,943 citations · Europe PMC · via azacitidine

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.